Background and objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is increasingly used for primary staging in prostate cancer. Owing to accurate detection of small metastases on PSMA-PET/CT, patient selection for robot-assisted radical prostatectomy (RARP) has likely changed. This study analyzes oncological outcomes in patients undergoing RARP and extended pelvic lymph node dissection (ePLND) after PSMA-PET/CT staging, compared with those without PSMA-PET/CT. Methods: Patients who underwent staging with PSMA-PET/CT before RARP and ePLND ("PSMA cohort"; 2016-2021) were compared with patients staged without PSMA-PET/ CT ("historical cohort"; 2013-2016). Propensity score matching using preoperative variables was performed to limit confounding. As primary outcome measure of biochemical recurrence (BCR)-free survival (BFS) was analyzed, with BCR defined as a prostate specific antigen value of >= 0.2 ng/ml or start of additional therapy after surgery. Key findings and limitations: After matching, 880 patients were included (440 in each cohort). The median follow-up was 35 mo (interquartile range 21-60) for the entire cohort. In the PSMA cohort, 126/440 patients (29%) experienced BCR versus 205/440 (47%) in the historical cohort (log-rank test p = 0.032). A multivariable Cox regression analysis showed an independent effect of preoperative PSMA-PET/CT staging on BFS (hazard ratio 0.70, 95% confidence interval 0.55-0.89, p = 0.0030). Conclusions and clinical implications: Patients who underwent staging with PSMA-PET/ CT had longer biochemical progression-free survival after RARP and ePLND than those without PSMA-PET/CT. This suggests that PSMA-PET/CT staging alters patient selection for RARP and ePLND, and is associated with improved early oncological outcomes for patients who still undergo surgery. Patient summary: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) at the diagnosis of prostate cancer leads to better visualization of metastases and therefore better selection of prostate cancer patients for surgery. Patients who underwent a PSMA-PET/CT scan at the time of diagnosis showed improved oncological outcomes, including longer progression-free survival and less prostate-specific antigen persistence after surgery. (c) 2024 Published by Elsevier B.V. on behalf of European Association of Urology.

BackgroundVarious risk classification systems (RCSs) are used globally to stratify newly diagnosed patients with prostate cancer (PCa) into prognostic groups.ObjectiveTo compare the predictive value of different prognostic subgroups (low-, intermediate-, and high-risk disease) within the RCSs for detecting metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) for primary staging, and to assess whether further subdivision of subgroups would be beneficial.Design, setting, and participantsPatients with newly diagnosed PCa, in whom PSMA-PET/CT was performed between 2017 and 2022, were studied retrospectively. Patients were stratified into risk groups based on four RCSs: European Association of Urology, National Comprehensive Cancer Network (NCCN), Cambridge Prognostic Group (CPG), and Cancer of the Prostate Risk Assessment.Outcome measurements and statistical analysisThe prevalence of metastatic disease on PSMA-PET/CT was compared among the subgroups within the four RCSs.Results and limitationsIn total, 2630 men with newly diagnosed PCa were studied. Any metastatic disease was observed in 35% (931/2630) of patients. Among patients classified as having intermediate- and high-risk disease, the prevalence of metastases ranged from approximately 12% to 46%. Two RCSs further subdivided these groups. According to the NCCN, metastatic disease was observed in 5.8%, 13%, 22%, and 62% for favorable intermediate-, unfavorable intermediate-, high-, and very-high-risk PCa, respectively. Regarding the CPG, these values were 6.9%, 13%, 21%, and 60% for the corresponding risk groups.ConclusionsThis study underlines the importance of nuanced risk stratification, recommending the further subdivision of intermediate- and high-risk disease given the notable variation in the prevalence of metastatic disease. PSMA-PET/CT for primary staging should be reserved for patients with unfavorable intermediate- or higher-risk disease.Patient summaryThe use of various risk classification systems in patients with prostate cancer helps identify those at a higher risk of having metastatic disease on prostate-specific membrane antigen positron emission tomography/computed tomography for primary staging.

BACKGROUND AND OBJECTIVE:Biochemical recurrence (BCR) of prostate cancer (PCa) after curative radiotherapy (RT) is defined according to the Phoenix criteria, which is a prostate-specific antigen (PSA) rise of ≥2.0 ng/ml above the PSA nadir. Prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) can identify PCa recurrences at very low PSA values. Our aim was to investigate the detection rate and extent of PCa recurrences using PSMA PET/CT after curative RT among patients with a PSA rise of ≥2.0 ng/ml above the nadir (Phoenix positive, Ph+) and patients not reaching this threshold (Phoenix negative, Ph-) and to compare therapeutic management and clinical outcomes in terms of time to androgen deprivation therapy (ADT) and castration-resistance PCa (CRPC), as well as overall survival. METHODS:We conducted a retrospective analysis of the Prostate Cancer Network Amsterdam (2015-2023) cohort of 568 patients who received curative-intent RT for PCa. Data on PSMA PET/CT outcomes, therapeutic management, and clinical follow-up were collected, including (re)initiation of ADT, progression to CRPC, and survival. Results were compared between groups using logistic regression and survival analyses. KEY FINDINGS AND LIMITATIONS:The study cohort comprised 222 patients (39.1%) classified as Ph- and 346 (60.9%) classified as Ph+. PSMA-avid lesions were detected in 170 Ph- patients (76.6%) and 322 (93.1%) Ph+ patients. In these groups, 75.9% of Ph- patients and 45.0% of Ph+ patients were eligible for local salvage therapy (odds ratio [OR 3.84]; p < 0.001). Distant metastases were less frequent in the Ph- group (n = 37, 21.8%) than in the Ph+ group (n = 157, 48.8%; OR 0.29; p < 0.001). Survival analyses revealed longer times to ADT (re)initiation and progression to CRPC, as well as lower overall mortality, in the Ph- group (log-rank p < 0.001). The retrospective study design is the main limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS:For patients with PCa recurrence, PSMA PET/CT can detect this recurrence in the majority of cases not meeting the Phoenix criteria for BCR. Early imaging detects recurrences at a less advanced disease stage, allowing potential salvage treatments. In addition, early PSMA PET/CT is associated with longer times to ADT (re)initiation and progression to CRPC, as well as longer overall survival. These positive clinical implications warrant confirmation of our results in prospective studies to reduce potential leadtime bias. PATIENT SUMMARY:We investigated early use of a special type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) in patients with suspicion of recurrence of their prostate cancer after radiotherapy. Early scans can detect recurrence before the cancer progresses to a more advanced stage.

Background/objectives: This study reassesses the diagnostic value of PSMA PET/CT in unfavorable intermediate-risk prostate cancer (PCa) and validates the Prostate Cancer Network the Netherlands (PCNN) subclassification. Subjects/methods: Men subjected to PSMA PET/CT were analyzed, evaluating the incidence of metastatic disease and its correlation with PCNN subgroups. Results: Metastatic disease was identified in 12.4% of patients. Higher PCNN subgroups correlated with increased metastatic potential; odds were significantly lower in low metastatic potential cases (OR: 0.19, 95% CI 0.06-0.62; p = 0.01). Conclusions: Our findings reaffirm PSMA PET/CT's diagnostic value in unfavorable intermediate-risk PCa and validate the PCNN subclassification, reducing scan burden by 48.1%.

Samenvatting Prostaatkanker is een van de meest voorkomende vormen van kanker bij mannen. Adequate stadiëring is van belang voor het bepalen van de therapie en de prognose. De prostaatspecifieke membraanantigeen (PSMA) positronemissietomografie/computertomografie (PET/CT) heeft een hogere diagnostische accuratesse voor het beoordelen van de aan-/afwezigheid van metastasen van prostaatkanker dan conventionele beeldvorming, bestaande uit CT-thorax/abdomen in combinatie met een botscan. Hierdoor worden er vaker metastasen gevisualiseerd en verandert bij een deel van de patiënten het stadium, meestal naar een hoger ziektestadium. De impact van deze stage shift op de prognose is nog niet uitgebreid onderzocht, maar geeft over het algemeen betere uitkomsten voor patiënten in hetzelfde stadium. Het is nog onduidelijk welke impact deze stage shift zou moeten hebben op de therapiekeuze van patiënten. Bij patiënten met gemetastaseerde prostaatkanker zouden de PSMA-bevindingen en behandelrespons op de PET/CT de kans op succesvolle behandeling kunnen voorspellen.

IntroductionRadiomics extracted from prostate-specific membrane antigen (PSMA)-PET modeled with machine learning (ML) may be used for prediction of disease risk. However, validation of previously proposed approaches is lacking. We aimed to optimize and validate ML models based on18F-DCFPyL-PET radiomics for the prediction of lymph-node involvement (LNI), extracapsular extension (ECE), and postoperative Gleason score (GS) in primary prostate cancer (PCa) patients.MethodsPatients with intermediate- to high-risk PCa who underwent18F-DCFPyL-PET/CT before radical prostatectomy with pelvic lymph-node dissection were evaluated. The training dataset included 72 patients, the internal validation dataset 24 patients, and the external validation dataset 27 patients. PSMA-avid intra-prostatic lesions were delineated semi-automatically on PET and 480 radiomics features were extracted. Conventional PET-metrics were derived for comparative analysis. Segmentation, preprocessing, and ML methods were optimized in repeated 5-fold cross-validation (CV) on the training dataset. The trained models were tested on the combined validation dataset. Combat harmonization was applied to external radiomics data. Model performance was assessed using the receiver-operating-characteristics curve (AUC).ResultsThe CV-AUCs in the training dataset were 0.88, 0.79 and 0.84 for LNI, ECE, and GS, respectively. In the combined validation dataset, the ML models could significantly predict GS with an AUC of 0.78 (p<0.05). However, validation AUCs for LNI and ECE prediction were not significant (0.57 and 0.63, respectively). Conventional PET metrics-based models had comparable AUCs for LNI (0.59,p>0.05) and ECE (0.66,p>0.05), but a lower AUC for GS (0.73,p<0.05). In general, Combat harmonization improved external validation AUCs (-0.03 to +0.18).ConclusionIn internal and external validation,18F-DCFPyL-PET radiomics-based ML models predicted high postoperative GS but not LNI or ECE in intermediate- to high-risk PCa. Therefore, the clinical benefit seems to be limited. These results underline the need for external and/or multicenter validation of PET radiomics-based ML model analyses to assess their generalizability.

You have accessJournal of UrologyCME1 Apr 2023MP40-15 THE DIAGNOSTIC VALUE OF PSMA PET/CT IN MEN WITH NEWLY DIAGNOSED INTERNATIONAL SOCIETY OF UROLOGICAL PATHOLOGY GRADE GROUP 3 INTERMEDIATE-RISK PROSTATE CANCER Marinus J. Hagens, Wietske I. Luining, Auke Jager, Maurits Wondergem, Maarten L. Donswijk, Zing Cheung, Daniela E. Oprea-Lager, André N. Vis, Pim J. van Leeuwen, and Henk G. van der Poel Marinus J. HagensMarinus J. Hagens More articles by this author , Wietske I. LuiningWietske I. Luining More articles by this author , Auke JagerAuke Jager More articles by this author , Maurits WondergemMaurits Wondergem More articles by this author , Maarten L. DonswijkMaarten L. Donswijk More articles by this author , Zing CheungZing Cheung More articles by this author , Daniela E. Oprea-LagerDaniela E. Oprea-Lager More articles by this author , André N. VisAndré N. Vis More articles by this author , Pim J. van LeeuwenPim J. van Leeuwen More articles by this author , and Henk G. van der PoelHenk G. van der Poel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Metastatic screening using prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is increasingly being adopted in urological practice. PSMA PET/CT has been shown to be of diagnostic value in men with high-risk prostate cancer (PCa), however, this has still not been demonstrated for men with International Society of Urological Pathology (ISUP) grade group (GG) 3 intermediate-risk PCa. This study aims to determine the diagnostic value of PSMA PET/CT within this subgroup of newly diagnosed ISUP GG3 intermediate-risk PCa patients. METHODS: Patients with newly diagnosed ISUP GG3 intermediate-risk PCa, in whom a PSMA PET/CT was performed as a primary staging modality, were retrospectively studied. PSMA PET/CT scans were performed in several diagnostic centers and revised/reported by expert nuclear medicine physicians within two high-volume PCa centers by expert nuclear medicine physicians. A multivariate logistic regression analysis, taking into account clinical, biochemical, pathological and radiological variables, was performed to identify potential independent predictors for metastatic disease on PSMA-PET/CT. RESULTS: In total, 396 men with newly diagnosed ISUP GG3 intermediate-risk PCa were studied. Metastatic disease was observed in 37/396 (9.3%) men, of whom 29/396 (7.3%) had molecular imaging locoregional lymph node metastases (miN1) and 16/396 (4.0%) had distant metastases (miM1). A radiological tumor stage ≥T3 on MRI (OR: 2.70 [95% CI: 1.25-5.87], p=0.01) and more than 75% positive prostate biopsies (OR: 5.00 [95% CI: 1.47-16.93], p=0.01) were found to be independently associated with metastatic disease on PSMA PET/CT (Table 1). CONCLUSIONS: Given that metastatic disease was observed in nearly one in ten men with biopsy ISUP GG3 intermediate-risk PCa, PSMA PET/CT is considered to be of diagnostic value within this population. Further stratification using the radiological tumor stage and the percentage of positive prostate biopsies could aid in identifying those patients at risk of having metastatic disease on PSMA PET/CT. Source of Funding: No funding was obtained © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e550 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marinus J. Hagens More articles by this author Wietske I. Luining More articles by this author Auke Jager More articles by this author Maurits Wondergem More articles by this author Maarten L. Donswijk More articles by this author Zing Cheung More articles by this author Daniela E. Oprea-Lager More articles by this author André N. Vis More articles by this author Pim J. van Leeuwen More articles by this author Henk G. van der Poel More articles by this author Expand All Advertisement PDF downloadLoading ...

Background and objectives: The association between prostate-specific antigen (PSA) level and probability of metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has not yet been established in patients with newly diagnosed prostate cancer (PCa). Our objective was to assess the probability of metastatic disease within different PSA ranges using PSMA PET/CT for initial staging of PCa, and to identify both the anatomical distribution and the predictors of metastases on PSMA PET/CT. Methods: In total, 2193 patients with newly diagnosed PCa were retrospectively studied. PSMA PET/CT was performed for staging purposes between January 2017 and May 2022. The proportion of patients with PSMA-avid metastases, stratified by PSA level, was studied. A vast majority of patients in whom at least one high-risk prognostic factor was present underwent PSMA PET/CT. A multivariable logistic regression analysis was performed to identify the predictors of metastases on PSMA PET/CT using clinical, biochemical, radiological, and pathological variables. Key findings and limitations: The median PSA level at PSMA PET/CT was 14.1 ng/ml. Any metastatic disease (miN1-M1a-c) was observed in 34.7% (763/2193) of all patients and distant metastases (miM1a-c) in 25.4% (557/2193) of patients. The presence of any metastatic disease increased with PSA levels, being 15.4% in men with PSA levels <10 ng/ml and 87.5% in men with PSA levels >100 ng/ml. The multivariable logistic regression analysis found significant associations between the presence of any metastatic disease and PSA subgroups, clinical tumor stage ≥T2, grade group >3, and radiological tumor stage ≥T3b. Conclusions and clinical implications: This is the first large epidemiological study in patients with PCa demonstrating the association between PSA subgroups and metastatic disease on modern imaging PSMA PET/CT. Data from this study can be used to counsel patients on the probability of metastatic disease at the time of PSA screening and to provide guidance on existing guidelines. Patient summary: The prostate-specific antigen level could be used to assess the risk of metastases on prostate-specific membrane antigen positron (PSMA) emission tomography/computed tomography (PET/CT). This knowledge is valuable for selecting patients who will benefit most from metastatic screening with PSMA PET/CT.

Our objective was to determine the diagnostic value of prostate-specific membrane antigen (PSMA) PET/CT in staging men with newly diagnosed unfavorable intermediate-risk prostate cancer (PCa). Methods: Patients with newly diagnosed unfavorable intermediate-risk PCa, in whom PSMA PET/CT was performed as a primary staging modality, were retrospectively studied. PSMA PET/CT was performed at several diagnostic centers and reported by expert nuclear medicine physicians within 2 high-volume PCa centers. A multivariate logistic regression analysis, taking into account clinical, biochemical, pathologic, and radiologic variables, was performed to identify potential independent predictors for metastatic disease on PSMA PET/CT. Results: In total, 396 men with newly diagnosed unfavorable intermediate-risk PCa were studied. Metastatic disease was observed in 37 (9.3%) men, of whom 29 (7.3%) had molecular imaging locoregional lymph node metastases (miN1) and 16 (4.0%) had distant metastases (miM1). A radiologic tumor stage of at least T3 on MRI (odds ratio, 2.72 [95% CI, 1.27-5.83]; P = 0.01) and more than 50% positive prostate biopsies (odds ratio, 3.87 [95% CI, 1.74-8.62]; P = 0.001) were found to be independently associated with metastatic disease on PSMA PET/CT. Conclusion: Given that metastatic disease was observed in nearly 1 in 10 men with newly diagnosed unfavorable intermediate-risk PCa, PSMA PET/CT is considered to be of diagnostic value within this population. Further stratification using the radiologic tumor stage and the percentage of positive prostate biopsies could aid in identifying those patients at risk of having metastatic disease on PSMA PET/CT.

Targeting the prostate-specific membrane antigen (PSMA) protein has become of great clinical value in prostate cancer (PCa) care. PSMA positron emission tomography/computed tomography (PET/CT) is increasingly used in initial staging and restaging at biochemical recurrence in patients with PCa, where it has shown superior detection rates compared to previous imaging modalities. Apart from targeting PSMA for diagnostic purposes, there is a growing interest in developing ligands to target the PSMA-protein for radioligand therapy (RLT). PSMA-based RLT is a novel treatment that couples a PSMA-antibody to (alpha or beta-emitting) radionuclide, such as Lutetium-177 (177Lu), to deliver high radiation doses to tumor cells locally. Treatment with 177Lu-PSMA RLT has demonstrated a superior overall survival rate within randomized clinical trials as compared to routine clinical care in patients with metastatic castration-resistant prostate cancer (mCRPC). The current review provides an overview of the literature regarding recent developments in nuclear medicine related to PSMA-targeted PET imaging and Theranostics.

Accurate staging of prostate cancer (PCa) at initial diagnosis and at biochemical recurrence is important to determine prognosis and the optimal treatment strategy. To date, treatment of metastatic PCa has mostly been based on the results of conventional imaging with abdominopelvic computed tomography (CT) and bone scintigraphy. However, these investigations have limited sensitivity and specificity which impairs their ability to accurately identify and quantify the true extent of active disease. Modern imaging modalities, such as those based on the detection of radioactively labeled tracers with combined positron emission tomography/computed tomography (PET/CT) scanning have been developed specifically for the detection of PCa. Novel radiotracers include 18F-sodium fluoride (NaF), 11C-/18F-fluorocholine (FCH), 18F-fluordihydrotestosterone (FDHT), 68Gallium and 18F-radiolabeled prostate-specific membrane antigen (e.g., 68Ga-PSMA-11, 18F-DCFPyL). PET/CT with these tracers outperforms conventional imaging. As a result of this, although their impact on outcome needs to be better defined in appropriate clinical trials, techniques like prostate-specific membrane antigen (PSMA) PET/CT have been rapidly adopted into clinical practice for (re)staging PCa. This review focuses on nuclear imaging for PCa bone metastases, summarizing the literature on conventional imaging (focusing on CT and bone scintigraphy-magnetic resonance imaging is not addressed in this review), highlighting the prognostic importance of high and low volume metastatic disease which serves as a driver for the development of better imaging techniques, and finally discussing modern nuclear imaging with novel radiotracers.